Bioabsorbable, biocompatible polymers for tissue engineering

ABSTRACT

Bioabsorbable biocompatible polymers which provide a good match between their properties and those of certain tissue structures are provided. The bioabsorbable biocompatible polymers can be prepared with tensile strengths, elongation to breaks, and/or tensile modulus (Young&#39;s modulus) values of the tissues of the cardiovascular, gastrointestinal, kidney and genitourinary, musculoskeletal, and nervous systems, as well as those of the oral, dental, periodontal, and skin tissues. Methods for processing the bioabsorbable biocompatible polymers into tissue engineering devices are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] Priority is claimed to U.S. provisional application Serial No.60/122,827, filed Mar. 4, 1999.

FIELD OF THE INVENTION

[0002] The present invention generally relates to bioabsorbable,biocompatible polymers and methods for making devices for tissueengineering and tissue regeneration from these materials.

BACKGROUND TO THE INVENTION

[0003] During the last 20 to 30 years, several bioabsorbable,biocompatible polymers have been developed for use in medical devices,and approved for use by the U.S. Food and Drug Administration (FDA).These FDA approved materials include polyglycolic acid (PGA), polylacticacid (PLA), Polyglactin 910 (comprising a 9:1 ratio of glycolide perlactide unit, and known also as VICRYL™), polyglyconate (comprising a9:1 ratio of glycolide per trimethylene carbonate unit, and known alsoas MAXON™), and polydioxanone (PDS). In general, these materialsbiodegrade in vivo in a matter of months, although certain morecrystalline forms biodegrade more slowly. These materials have been usedin orthopedic applications, wound healing applications, and extensivelyin sutures after processing into fibers. More recently, some of thesepolymers also have been used in tissue engineering applications.

[0004] Tissue engineering has emerged as a multi-disciplinary fieldcombining biology, materials science, and surgical reconstruction, toprovide living tissue products that restore, maintain, or improve tissuefunction. The need for this approach has arisen primarily out of a lackof donor organs and tissues, but also because it offers the promise ofbeing able to dramatically expand the ability to repair tissues anddevelop improved surgical procedures.

[0005] In general, three distinct approaches currently are used toengineer new tissue. These are (1) infusion of isolated cells or cellsubstitutes, (2) use of tissue inducing materials and/or tissueregeneration scaffolds (sometimes referred to as guided tissue repair),and (3) implantation of cells seeded in scaffolds (either prior to orsubsequent to implantation). In the third case, the scaffolds may beconfigured either in a closed manner to protect the implanted cells fromthe body's immune system, or in an open manner so that the new cells canbe incorporated into the body.

[0006] In open scaffold systems and guided tissue repair, tissueengineering devices have normally been fabricated from natural proteinpolymers such as collagen, or from the synthetic polymers listed above,which in both cases degrade over time and are replaced by new tissue.While some of these materials have proven to be good substrates for celland tissue growth, and provide good scaffolding to guide and organizethe regeneration of certain tissues, they often do not have the specificmechanical requirements that the scaffold needs to provide until the newtissue is developed and able to take over these functions. Thesematerials may also be difficult to process and fabricate into thedesired form, handle poorly in the operating room, be difficult tosuture, and sometimes fall apart prematurely. For example, it has beenreported that tissue engineered heart valve leaflet scaffolds derivedfrom polyglactin and PGA are too stiff and cause severe pulmonarystenosis when implanted in sheep (Shinoka, et al., “New frontiers intissue engineering: tissue engineered heart valves” in SyntheticBioabsorbable Polymer Scaffolds (Atala & Mooney, eds.) pp. 187-98(Birkhauser, Boston, 1997)).

[0007]FIG. 1, which plots the tensile strength and elongation to breakvalues for representative FDA approved (compression molded)bioabsorbable biocompatible polymers against these values for differenttissue structures, reveals a significant mismatch between the mechanicalproperties of these polymers and the different tissue structures. Inparticular, it is apparent that the existing bioabsorbable biocompatiblepolymers are stiff, inelastic materials, with elongations to break ofaround 25%, yet many tissues are much more flexible, elastic, and havelonger elongation to break values. Accordingly, the biomaterial productscurrently used in temporary scaffolds for regenerating human tissues donot exhibit the same multi-axial physical and mechanical properties asnative tissues, which are hierarchical, three-dimensional structures(see abstract of an award by the Advanced Technology Program to Johnsonand Johnson Corporate Biomaterials Center, October 1997).

[0008] Attempts have been made to develop new bioabsorbablebiocompatible polymers with more flexible, elastomeric properties. Oneapproach has been to incorporate lactide or glycolide and caprolactonejoined by a lysine-based diisocyante into a polyurethane (Lamba, et al.,“Degradation of polyurethanes” in Polyurethanes in BiomedicalApplications, pp. 199-200 (CRC Press LLC, Boca Raton, Fla., 1998).However, these crosslinked polyurethane networks cannot be processed bystandard techniques such as solution casting or melt processing,limiting their usefulness. There is also no evidence that thepolyurethane segments are completely biodegraded in vivo. A commercialmaterial, known as TONE™, has also been evaluated as an elastomericimplant material. However, this material degrades in vivo very slowly,and therefore has limited application (Perrin, et al.,“Polycaprolactone” in Handbook of Bioabsorbable Polymers (Domb, et al.,eds.) pp. 63-76 (Harwood, Amsterdam, 1997)). Another approach has beento synthesize protein-based polymers, particularly polymers containingelastomeric polypeptide sequences (Wong, et al., “Synthesis andproperties of bioabsorbable polymers used as synthetic matrices fortissue engineering” in Synthetic Bioabsorbable Polymer Scaffolds (Atala& Mooney, eds.) pp. 51-82 (Birkhauser, Boston, 1997). However, thesematerials are not reported to biodegrade in vivo, although cells caninvade matrices derived from these materials. They also lack theadvantages of thermoplastic polymers in fabrication of devices.

[0009] U.S. Pat. Nos. 5,468,253 and 5,713,920, both to Bezwada et al.,disclose bioabsorbable elastomeric materials which are used to formdevices that, based on in vitro data, are alleged to completelybioabsorb within one year or six months. However, deGroot et al.,Biomaterials, 18:613-22 (1997) provides in vivo data for these materialsand reports that the implanted material fragmented after 56 weeks intowhite crystalline-like fragments. It is suspected that these fragmentsare crystalline poly-L-lactide, which is very slow to degrade.Nonetheless, whatever the composition of the fragments, the material isnot completely bioabsorbed after one year in vivo. These materials alsotypically are difficult to process and may have poor shelf stability.

[0010] Thus, while the current bioabsorbable biocompatible polymersoffer a range of useful properties for certain medical applications, itis desirable to develop methods to prepare bioabsorbable biocompatiblepolymers that significantly extend the range of properties available. Itwould thus be desirable to develop methods for preparing bioabsorbablebiocompatible polymers with mechanical properties closer to those oftissue, particularly soft tissues. It would also be desirable to developmethods for making bioabsorbable biocompatible materials which can bereadily processed, and fabricated into tissue engineering devices thatcan be easily implanted.

[0011] It is therefore an object of this invention to provide methodsfor preparing bioabsorbable biocompatible polymers with mechanicalproperties that provide a better match with those of tissue structures.

[0012] It is a further object of this invention to provide newcompositions with mechanical properties that provide a better match withthose of tissue structures.

[0013] It is another object of this invention to provide methods forfabricating devices from these compositions.

SUMMARY OF THE INVENTION

[0014] Bioabsorbable biocompatible polymers are selected based on theirphysical and/or mechanical properties to correspond to the physicalproperties of tissues to be regenerated or constructed. Physicalproperties include elasticity, strength, flexibility, andprocessibility. These properties can be measured by determining factorssuch as tensile strength, elongation or extension to break, and Youngsmodulus. In a preferred embodiment, the polymers have an extension tobreak over 25%, tensile strength less than 10,000 psi, Youngs modulusless than 100,000 psi, glass transition temperature less than 20° C.,and melting temperature less than 190° C. In one embodiment, thebioabsorbable biocompatible polymers can be prepared with tensilestrengths equivalent to the tensile strengths of the tissues of thecardiovascular, gastrointestinal, kidney and genitourinary,musculoskeletal, and nervous systems, as well as those of the oral,dental, periodontal, and skin tissues. In another embodiment, thebioabsorbable biocompatible polymers can be prepared with elongations tobreak equivalent to the elongations to break of the same tissues. Instill another embodiment, the bioabsorbable biocompatible polymers canbe prepared with tensile modulus (Young's modulus) values equivalent tothese tissues.

[0015] Methods for processing the bioabsorbable biocompatible polymersinto tissue engineering devices are also described.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016]FIG. 1 is a graph comparing the mechanical properties of PGA, PLA,polyglactin, polyglyconate, and polydioxanone with those of differenttissue structures.

[0017]FIG. 2 is a graph comparing the mechanical properties ofbioabsorbable polymers described herein with the mechanical propertiesof different tissues or tissue structures.

DETAILED DESCRIPTION OF THE INVENTION

[0018] Polymers are provided which are bioabsorbable, biocompatible, andhave mechanical properties similar to the physical and/or mechanicalproperties of tissue structures, including stress, strain,stress-strain, stress-strain hysteresis, stress-strain relaxation,viscoelasticity, contraction stress, resting stress, Young's modulus,tensile strength, durability, yield point, failure strength, toughness,ductility, softness, hardness, creep, elastic deformation, wearresistance, shear failure, roughness, compressive strength, loadcapacity, modulus of elasticity, ultimate compressive strength, yieldstrength, stress-strain relationship, scratch resistance, abrasionresistance, flexural modulus, shear modulus, contact angle, surfacetension, adhesive strength, surface free energy, bending strength, shearstrength, bonding strength, bending strength, bending stiffness,compressive modulus, bending modulus, fracture toughness, elongation,fiber strength, fiber modulus, fiber elongation, thermal expansioncoefficient, fracture toughness, static and dynamic elasticity,longitudinal stretch, stress, and strain, radial stretch, stress andstrain, circumferential stretch, stress and strain, ultimate elongation,viscosity, expansion, static and kinetic coefficients of friction,plasticity, axial tension, shock absorbance, bearing strength,formability, rigidity, stress rupture, bend radius, impact strength, andfatigue strength. In a preferred embodiment, the polymers haveelongations to break of more than 25%, and/or tensile modulus valuesless than 500,000 psi. In another preferred embodiment, the polymers arefabricated into medical devices using standard polymer processingtechniques, and used as tissue engineering devices to provide livingtissue products that restore, maintain, or improve tissue function, forexample, in the cardiovascular, gastrointestinal, kidney andgenitourinary, musculoskeletal, and nervous systems, as well as those ofthe oral, dental, periodontal, and skin tissues.

[0019] I. Polymers

[0020] The polymers described herein may be prepared by synthetic ornatural methods. However, the method must provide the desired polymer ina form sufficiently pure for use as an implantable material. The polymershould not contain any undesirable residues or impurities which couldelicit an undesirable response either in vitro in the case of acell-seeded construct or in vivo.

[0021] The polymers may be prepared from any combination of monomericunits. These units must, however, be capable of biodegrading in vivo tonontoxic compounds, which can optionally be excreted or furthermetabolized. The combination of units in the polymer must also bebiocompatible, and not elicit an undesirable biological response uponimplantation. The polymer may be biodegraded in vivo by any means,including hydrolysis, enzymatic attack, a cell-mediated process, or byany other biologically mediated process. It is considered desirable fortissue engineering applications that the polymer scaffold serve as atransitional construct, and thus be fully degraded once the new tissueis able to take over the function of the scaffold. Since the rates atwhich different new tissues are likely to be able to assume their newfunction will vary, it is desirable to have polymers with a range ofdegradation rates as well as a range of different properties. Generally,however, preferred polymers will degrade in a matter of weeks to months,preferably less than one year, rather than several years.

[0022] The mechanical properties of the polymer are designed to meet theneeds of the particular tissue engineering application. Thus, accordingto the method described herein for preparing bioabsorbable biocompatiblepolymers, the monomeric units can be selected to provide uponcombination of the correct ratios of these monomeric units the desiredproperty or property set. If necessary, the monomeric units may becombined in a specific order as in, for example, a block copolymer, oralternatively they can be assembled in a random manner. They may also beprepared with different molecular weights to achieve the correctperformance.

[0023] In a preferred method as described herein, the monomeric unitsare hydroxy acids, and the polymers are polyesters. The distance betweenthe hydroxy group and the acid group can be small or large, however,monomers are preferably 2-, 3-, 4-, 5-, or 6-hydroxy acids. The hydroxyacids may optionally contain other functional groups and be substitutedat any position, including heteroatoms between the hydroxy and acidgroups. These hydroxy acids may be polymerized either using syntheticmethods or preferably using biological methods. In the latter case, thehydroxy acids may be derived in vivo from a non-hydroxy acid source.

[0024] Suitable methods for preparing the polyesters are described inWilliams, S. F. and Peoples, O. P. CHEMTECH, 26:38-44 (1996), Williams,S. F. and Peoples, O. P., Chem. Br., 33:29-32 (1997), U.S. Pat. No.4,910,145 to Holmes, P. A. and Lim, G. B.; Byrom, D., “MiscellaneousBiomaterials,” in D. Byrom, Ed., “Biomaterials” MacMillan Publishers,London, 1991, pp. 333-59; Hocking, P. J. and Marchessault, R. H.“Biopolyesters”, G. J. L. Griffin, Ed., “Chemistry and Technology ofBioabsorbable Polymers,” Chapman and Hall, London, 1994, pp.48-96;Holmes, P. A., “Biologically Produced (R)-3-hydroxyalkanoate Polymersand Copolymers,” in D. C. Bassett Ed., “Developments in CrystallinePolymers,” Elsevier, London, Vol. 2, 1988, pp. 165; Lafferty et al.,“Microbial Production of Poly-β-hydroxybutyric acid,” H. J. Rehm and G.Reed, Eds., “Biotechnology”, Verlagsgesellschaft, Weinheim, Vol. 66,1988, pp. 135-76; Müller and Seebach, Angew. Chem. Int. Ed. Engl.32:477-502 (1993); Steinbüchel, A. “Polyhydroxyalkanoic Acids,” in D.Byrom Ed., “Biomaterials”, MacMillan Publishers, London, 1991, pp.123-213; Steinbüchel and Wiese, Appl. Microbiol. Biotechnol., 37:691-697(1992); U.S. Pat. Nos. 5,245,023; 5,250,430; 5,480,794; 5,512,669;5,534,432; Agostini, D. E. et al., Polym. Sci., Part A-1, 9:2775-87(1971); Gross, R. A. et al, Macromolecules, 21:2657-68 (1988); Dubois,P. I. et al., Macromolecules, 26:4407-12 (1993); Le Borgne, A. andSpassky, N., Polymer, 30:2312-19 (1989); Tanahashi, N. and Doi, Y.,Macromolecules, 24:5732-33 (1991); Hori, Y. M. et al., Macromolecules,26:4388-90 (1993); Kemnitzer, J. E. et al., Macromolecules, 26:1221-1229(1993); Hori, Y. M. et al., Macromolecules, 26:5533-34 (1993); Hocking,P. J. and Marchessault, R. H., Polym. Bull., 30:163-70 (1993); Xie, W.et al., Macromolecules, 30:6997-98 (1997), U.S. Pat. No. 5,563,239 toHubbs, J. C. and Harrison, M. N., and Braunegg, G. et al., J.Biotechnol. 65:127-61 (1998), and Madison & Huisman, Microb. Mol. Biol.Rev. 63:21-53 (1999).

[0025] In another preferred method described herein, the bioabsorbablebiocompatible polymers are polyesters including one or more linkages inthe main polymer chain which are not ester linkages. These linkagesshould be susceptible to cleavage in vivo. Suitable non-ester linkagesmay include amides, urethanes, carbonates, iminocarbonates, oxalates,oxamates, orthoesters, anhydrides, phosphazenes, glycosides, and ethers.Incorporation of such chemistries can be used to alter biodegradationrates, tailor mechanical, surface, or other properties of the polymer,improve processibility and handling of the materials, and/or to providemethods for attachment of other compounds to the polymers.

[0026] The bioabsorbable biocompatible polymers described herein mayoptionally be further modified either prior to or subsequent tofabrication. Representative modifications include derivatization,surface treatments, coatings, coupling of other compounds particularlybiologically active agents.

[0027] II. Mechanical Properties and Polymer Compositions

[0028] The bioabsorbable biocompatible polymers described herein may beprepared with mechanical properties that resemble those of tissue. Theseproperties are achieved by preparing the polymers with differentcompositions and ratios of monomeric constituents. For example, polymerswith tensile strengths near or equal to that of tendon and dentin can beprepared by polymerizing 4-hydroxybutyric acid. By incorporatingR-3-hydroxybutyric acid with 4-hydroxybutyric acid into the same polymeras a random copolymer, it is possible to prepare a material with atensile strength near or equal to that of cortical bone. Usingcombinations of R-3-hydroxyoctanoate and R-3-hydroxyhexanoate, it ispossible to prepare a copolymer with a tensile strength near or equal tothat of skin and enamel. Other monomers may be incorporated to increaseor decrease the tensile strengths of the bioabsorbable biocompatiblepolymers.

[0029] The elongation to break of the bioabsorbable biocompatiblepolymers may also be controlled and tailored to those of tissue in asimilar manner. For example, the homopolymer of R-3-hydroxybutyric acidhas an elongation to break of around 5%, close to tendon. Thiselongation to break may be progressively increased to values forcartilage, cardiac muscle, cardiovascular tissues, skin, aorta,urological tissue, in fact virtually any tissue, by incorporating aco-monomer, 4-hydroxybutyric acid, with R-3-hydroxybutyric acid into acopolymer. A copolymer comprising 3-8% 4-hydroxybutyric acid polymerizedwith 3-hydroxybutyric acid has an extension to break of 45% to over100%, which are similar values to those of cardiac muscle, skin,urological and cardiovascular tissues including blood vessels and heartvalves.

[0030] In the same manner, it is also possible to prepare bioabsorbablebiocompatible polymers described herein with a range of tensile modulusvalues (Youngs modulus) that match those of tissue structures. Forexample, depending upon the age of the person, skin has a tensilemodulus value ranging from about 2,000 psi for young children to around18,000 psi for older people. According to the method described herein,it is possible to produce a copolymer of R-3-hydroxyoctanoic acid andR-3-hydroxyhexanoic acid with a Youngs modulus value of around1,000-2,000 psi, and a copolymer of R-3-hydroxybutyric acid and4-hydroxybutyric acid with a Youngs modulus ranging from 3,000 psi to22,000 psi as the percentage of 4-hydroxybutyric acid is increased from78% to 100%. Other compositions can be used for applications requiringhigher Youngs modulus values. For example, the homopolymer ofR-3-hydroxybutyric acid has a Youngs modulus value of around 500,000psi.

[0031] Thus, by using combinations of different hydroxy acid monomers,it is possible to prepare bioabsorbable biocompatible polymers with awide range of Youngs modulus values that encompass different tissuestructures.

[0032] By using a similar approach of combining appropriate monomerunits, bioabsorbable biocompatible polymers can be produced that haveother desirable mechanical properties and even desirable barrierproperties that provide a good compliance match with tissue. Examples ofother mechanical properties which can be prepared according to themethod described herein include, but are not limited to, compressivestrength, hardness, burst strength, impact strength, toughness, as wellas other viscoelastic elastic properties. Examples of desirable barrierproperties include water and fluid barrier properties, moisture vaporbarrier properties, and gas barrier properties.

[0033] In some embodiments, it may be desirable to produce abioabsorbable biocompatible polymer with two or more mechanicalproperties providing a good compliance match with a specific tissuestructure. For example, tendon has a tensile strength of around 6,000psi and an elongation to break of 10%. According to the method describedherein, a bioabsorbable biocompatible polymer can be produced comprising10% R-3-hydroxypentanoic acid and R-3-hydroxybutyric acid, withapproximately the same tensile strength of about 6,000 psi and anextension to break of 10% as tendon. Similarly, other combinations ofone, two, or more monomeric units can be used to provide bioabsorbablebiocompatible polymers with two or more of the desired mechanicalproperties of a particular tissue structure.

[0034] III. Fabrication of Bioabsorbable Biocompatible Devices

[0035] The bioabsorbable biocompatible polymer compositions are usefulfor preparing a variety of medical devices. Examples of applications ofsuch devices include tissue engineering scaffold, guided tissue repairmaterial, wound dressing, drug delivery vehicle, anti-adhesion material,cell encapsulation material, coating, implant, stent, orthopaedicdevice, prosthetic, adhesives, diagnostics, sutures, surgical meshes,staples, meniscus repair and regeneration devices, screws (interferencescrews and meniscal screws), bone plates and plating systems,cardiovascular patches, pericardial patches, slings, pins, anti-adhesionbarriers, articular cartilage repair devices, nerve guides, tendon andligament repair devices, atrial septal defect pathces, bulking andfilling agents, vein valves, bone marrow scaffolds, bone graftscaffolds, skin substitutes, dural substitutes, ocular implants, spinalfusion cages, and muscular implants (cardiac and skelatal). Thesematerials may be used alone, with additives or in combinations withthemselves or other materials. Additives and other materials may includethose components added for the purpose of further modification of aparticular property or properties, and/or those components which arebiologically active such as cell attachment factors, growth factors,peptides, antibodies and their fragments.

[0036] In general, a key advantage described herein is that thebioabsorbable biocompatible polymers can be processed using conventionalpolymer processing techniques. Many of the materials are thermoplastics,and are thus amenable to standard methods for processing such materials.Such methods are well known to those skilled in the art, and includesuch methods as melt processing, solvent processing, leaching, foaming,extrusion, injection molding, compression molding, blow molding, spraydrying, extrusion coating, spinning of fibers and subsequent processinginto woven or non-woven constructs.

[0037] A preferred fabricated form of the compositions is a porous(fibrous) construct, particularly ones which can be used as tissueengineering scaffolds, and guided tissue repair meshes and matrices.This construct or matrix may be derived by any suitable method,including salt leaching, sublimation, solvent evaporation, spray drying,foaming, processing of the materials into fibers and subsequentprocessing into woven or non-woven devices. Such constructs can be usedin tissue engineering applications of the tissues of the cardiovascular,gastrointestinal, kidney and genitourinary, musculoskeletal, and nervoussystems, as well as those of the oral, dental, periodontal, and skintissues. Examples of such constructs can be used to prepare tissueengineering scaffolds for both hard and soft tissues. Representativetissue types include, but are not limited to, cardiovascular (includingblood vessel, artery, and heart valve), cornea and other ocular tissues,pancreas, alimentary tract (e.g., esophagus and intestine), ureter,bladder, skin, cartilage, dental, gingival tissue, bone, liver, kidney,genital organs (including penis, urethra, vagina, uterus, clitoris, andtestis), nerve, spinal cord, meniscus, pericardium, muscle (e.g.,skeletal), tendon, ligament, trachea, phalanges and small joints, fetal,and breast.

[0038] A further advantage of some of the compositions described hereinis their ability to be sterilized by radiation sources, in addition toethylene oxide. Moreover, certain compositions described herein have theadditional advantage of good shelf stability, resistance to hydrolysisby water and moisture, and thus less restrictive packaging needs toexclude moisture after preparation, fabrication, and during storage.

[0039] Another advantage to using the compositions described herein isthe ability to create three dimensional polymer scaffold systems withproperties in different regions. This can be achieved by combining thecompositions described herein either in different forms, or combiningdifferent compositions to make one or more forms. For example, aspecific composition may be processed into a fibrous form, and thensubsequently processed and combined with another different fibrous ornon-fibrous composition. Such combinations may be achieved by weaving,melt processing, solvent processing, coating, and other methods known tothose skilled in the art.

[0040] Those skilled in the art will recognize, or be able to ascertainusing no more than routine experimentation, many equivalents to thespecific embodiments of the invention described herein. The referencescited herein arc hereby incorporated by reference.

[0041] Modifications and variations of the present invention will beobvious to those of skill in the art from the foregoing detaileddescription. Such modifications and variations are intended to comewithin the scope of the following claims.

I claim:
 1. A composition or device for use in tissue engineeringcomprising a bioabsorbable biocompatible polymer comprisingpolyhydroxyalkanoate, wherein the polymer has one or more mechanicalproperties selected from the group consisting of stress, strain,stress-strain, stress-strain hysteresis, stress-strain relaxation,viscoelasticity, contraction stress, resting stress, Young's modulus,tensile strength, durability, yield point, failure strength, toughness,ductility, softness, hardness, creep, elastic deformation, wearresistance, shear failure, roughness, compressive strength, loadcapacity, modulus of elasticity, ultimate compressive strength, yieldstrength, stress-strain relationship, scratch resistance, abrasionresistance, flexural modulus, shear modulus, contact angle, surfacetension, adhesive strength, surface free energy, bending strength, shearstrength, bonding strength, bending strength, bending stiffness,compressive modulus, bending modulus, fracture toughness, elongation,fiber strength, fiber modulus, fiber elongation, thermal expansioncoefficient, fracture toughness, static and dynamic elasticity,longitudinal stretch, stress, and strain, radial stretch, stress andstrain, circumferential stretch, stress and strain, ultimate elongation,viscosity, expansion, static and kinetic coefficients of friction,plasticity, axial tension, shock absorbance, bearing strength,formability, rigidity, stress rupture, bend radius, impact strength, andfatigue strength, equivalent to the same properties of a differentiatedtissue or tissue structure, wherein the polymer comprisespolyhydroxyalkanoate.
 2. The composition of claim 1 wherein the polymerdegrades in vivo in less than one year.
 3. The composition of claim 1wherein the polymer has an extension to break of over 25%.
 4. Thecomposition of claim 3 wherein the polymer is in the form of a fiber andthe extension to break is over 45%.
 5. The composition of claim 1wherein the polymer has a tensile strength less than 10,000 psi.
 6. Thepolymer of claim 5 wherein the polymer is in the form of a fiber and thetensile strength is less than 50,000 psi.
 7. The composition of claim 1wherein the polymer has a Youngs modulus of less than 100,000 psi. 8.The polymer of claim 7 wherein the polymer is in the form of a fiber andthe Youngs modulus is less than 200,000 psi.
 9. The composition of claim1 wherein the polymer has a melting temperature less than 190° C. 10.The composition of claim 1 wherein the polymer has a glass transitiontemperature less than 20° C.
 11. The composition of claim 1 wherein thepolymer has two or more properties selected from the group consisting ofextension to break over 25%, tensile strength less than 10,000 psi,Youngs modulus less than 100,000 psi, glass transition less than 20° C.,and melting temperature less than 190° C.
 12. The composition of claim 1wherein the tissue is selected from the group consisting ofcardiovascular, gastrointestinal, kidney, genitourinary,musculoskeletal, nervous, oral, breast, periodontal, and skin.
 13. Thecomposition of claim 1 wherein the mechanical property is selected fromthe group consisting of tensile strength, Youngs modulus, elongation tobreak, hardness, compressive strength, burst strength, toughness, andimpact strength.
 14. The composition of claim 1 wherein the tissue iscartilage and the polymer has a tensile strength of 435 psi±125%. 15.The composition of claim 1 wherein the tissue is skin and the polymerhas a tensile strength of 1,100 psi±25%.
 16. The composition of claim 1wherein the tissue is tendon and the polymer has a tensile strength of7,700 psi±25%.
 17. The composition of claim 1 wherein the tissue isaorta and the polymer has a tensile strength of 160 psi±25%.
 18. Thecomposition of claim 1 wherein the tissue is cardiac muscle and thepolymer has a tensile strength of 16 psi±25%.
 19. The composition ofclaim 1 wherein the tissue is bone and a polymer has a tensile strengthof 10,000 psi±25%.
 20. The composition of claim 1 wherein the tissue isenamel and the polymer has a tensile strength of 1,600 psi±25%.
 21. Thecomposition of claim 1 wherein the tissue is skin and the polymer has anultimate elongation of 78%±25%.
 22. The composition of claim 1 whereinthe tissue is tendon and the polymer has an ultimate elongation of10%±25%.
 23. The composition of claim 1 wherein the tissue is cartilageand polymer has an ultimate elongation of 30%±25%.
 24. The compositionof claim 1 wherein the tissue is heart and the polymer has an ultimateelongation of 10-15%±25%.
 25. The composition of claim 1 wherein thetissue is aorta and the polymer has an ultimate elongation in thetransverse and longitudinal directions of 77-81%±25%.
 26. Thecomposition of claim 1 wherein the tissue is skin and the polymer has aYoungs modulus of 2,000-18,000 psi±25%.
 27. A device comprising abioabsorbable biocompatible polymer with one of more mechanicalproperties equivalent to a specific tissue or tissue structure, whereinthe device is selected from the group consisting of a tissue engineeringscaffold, guided tissue repair material, wound dressing, drug deliveryvehicle, anti-adhesion material, cell encapsulation material, coating,implant, stent, orthopaedic device, prosthetic, adhesive, diagnostic,sutures, surgical meshes, staples, meniscus repair and regenerationdevices, screws (interference screws and meniscal screws), bone platesand plating systems, cardiovascular patches, pericardial patches,slings, pins, anti-adhesion barriers, articular cartilage repairdevices, nerve guides, tendon and ligament repair devices, atrial septaldefect pathces, bulking and filling agents, vein valves, bone marrowscaffolds, bone graft scaffolds, skin substitutes, dural substitutes,ocular implants, spinal fusion cages, and muscular implants (cardiac andskelatal).
 28. The device of claim 27 wherein the device is a tissueengineering scaffold or matrix.
 29. The device of claim 28 wherein thepolymer degrades in vivo in less than two years.
 30. The device of claim28 wherein the tissue engineering scaffold which has differentproperties in different regions.
 31. The device of claim 28 wherein thescaffold or matrix is flexible.
 32. The device of claim 28 wherein thetissue is heart valve or blood vessel.
 33. The device of claim 28wherein the tissue engineering scaffold or matrix is for tissueengineering of musculoskeletal tissue.
 34. The device of claim 28wherein the tissue is selected from the group consisting of cartilage,tendon, ligament, and bone.
 35. The device of claim 28 wherein thetissue engineering scaffold or matrix is for tissue engineering ofgenitourinary tissue.
 36. The device of claim 28 wherein the tissueforms a structure selected from the group consisting of bladder, ureter,and urethra.
 37. The device of claim 28 for tissue engineering ofgingiva.
 38. The device of claim 28 seeded with cells for implantation.39. The device of claim 28 further comprising materials selected fromthe group consisting of other polymers, compounds, additives,biologically active substances, growth factors, cell attachment factors,and drugs.
 40. A method for producing a bioabsorbable biocompatiblepolymer composition comprising: selecting a tissue structure andmeasuring one or more mechanical properties selected from the groupconsisting of stress, strain, stress-strain, stress-strain hysteresis,stress-strain relaxation, viscoelasticity, contraction stress, restingstress, Young's modulus, tensile strength, durability, yield point,failure strength, toughness, ductility, softness, hardness, creep,elastic deformation, wear resistance, shear failure, roughness,compressive strength, load capacity, modulus of elasticity, ultimatecompressive strength, yield strength, stress-strain relationship,scratch resistance, abrasion resistance, flexural modulus, shearmodulus, contact angle, surface tension, adhesive strength, surface freeenergy, bending strength, shear strength, bonding strength, bendingstrength, bending stiffness, compressive modulus, bending modulus,fracture toughness, elongation, fiber strength, fiber modulus, fiberelongation, thermal expansion coefficient, fracture toughness, staticand dynamic elasticity, longitudinal stretch, stress, and strain, radialstretch, stress and strain, circumferential stretch, stress and strain,ultimate elongation, viscosity, expansion, static and kineticcoefficients of friction, plasticity, axial tension, shock absorbance,bearing strength, formability, rigidity, stress rupture, bend radius,impact strength, and fatigue strength, equivalent to the same propertiesof a differentiated tissue or tissue structure, and selecting from acombination of monomers that can be polymerized to make a polymer, oneor more monomers which when linked in a polymeric form, have themechanical property or properties of the tissue or tissue structure. 41.The method of claim 40 wherein the tissue structure is selected from thegroup consisting of cardiovascular structures including heart valves andblood vessels, gastrointestinal structures, kidney, genitourinarystructures including bladder, ureter, and urethra, musculoskeletalstructures including bone, cartilage, tendon, and ligament, nervoussystem structures, oral tissues, periodontal tissues, and skin tissue.42. The method of claim 40 wherein the monomers are selected fromhydroxy acids.
 43. The method of claim 40 wherein the polymer isselected from the group consisting of polyester, poly(orthoester),polyanhydride, polyphosphazene, polyesteramide, polypeptide, polyamide,polydihydropyran, and polycyanoacrylate.
 44. The method of claim 40wherein the polymercontains one or more linkages selected from the groupconsisting of ester, amide, urethane, carbonate, iminocarbonate,oxalate, oxamate, orthoester, anhydride, phosphazene, glycoside, andether linkages.